Nicotinic Acid Increases Lipoprotein Lipase Activity in Skeletal Muscle, But Only When Sedentary

Abstract

1015 Nicotinic acid treatment (niacin) is known to reduce coronary heart disease and all cause mortality. An important mechanism thought to be mediating the cardioprotective effect of niacin is the marked lowering of plasma triglyceride rich lipoproteins and the elevation of high density lipoprotein concentrations. Because skeletal muscle lipoprotein lipase (LPL) is a key enzyme is the catabolism of plasma triglycerides and plays an important role in HDL metabolism, niacin may be mediating some of its effects on lipoprotein metabolism via LPL regulation. PURPOSE: The purpose of this study was to determine if nicotinic acid affects muscle LPL activity. METHODS: As muscle LPL regulation is highly dependent upon recent contractile activity (Bey and Hamilton, J.Physiol. 551, 2003), we tested the effect of nicotinic acid on muscle LPL in 3–4 month old female ambulatory rats that have normally high muscle LPL activity and in these rats when the skeletal muscle was made physically inactive for 11 hours by hindlimb unloading. Nicotinic acid plus saline or saline alone was infused i.p. throughout the 11 hours in both ambulatory and hindlimb unloaded rats. After 11 hours, rats were anesthetized and soleus and red gastrocnemius (RG) muscles were harvested and analyzed for heparin releasable LPL (HR-LPL) activity. RESULTS: In agreement with our recent findings, physical inactivity markedly reduced soleus and RG HR-LPL activity by 89 and 90%, respectively (both p < 0.01), compared to ambulatory levels. The treatment of ambulatory healthy rats with nicotinic acid did not affect HR-LPL activity in either soleus or RG. Remarkably, nicotinic acid treatment of hindlimb unloaded rats resulted in 9 and 7 fold greater soleus and RG HR-LPL activity, respectively, than treatment with saline alone (both p < 0.01). Therefore, nicotinic acid completely restored soleus HR-LPL activity to 100% of ambulatory rat levels and partially restored RG to 68% of HR-LPL activity in ambulatory rats. CONCLUSIONS: Nicotinic acid can have a marked effect on skeletal muscle LPL regulation, presumably through reduction of adipose tissue lipolysis, and this ability is very dependent on recent contractile activity. Supported by NIH HL70482-01.